The Vermont Pulmonary SCOR has developed a coordinated, comprehensive and systematic approach for studying mechanisms of pulmonary interstitial remodeling. This involves multidisciplinary applications of forefront research technologies from cell and molecular biology to sophisticated patient diagnosis, management and care. Program goals are to define organ, tissue and cell function as modified by specific agents involved in the etiology of occupational and immunologic lung disease to improve the scientific basis of diagnosis, management and treatment. Studies of specific human interstitial diseases will focus on the tissue and cellular pathology of developing and endpoint disease. Parallel studies of animal models of silica and asbestos mediated lung injury will focus on connecting the events of injury, inflammation and eventual tissue remodeling. Finally, specific cell culture and co-culture systems will be used to explore the cell biology of the remodeling process as it pertains to the vasculature and interstitium. Studies will define the roles of a limited number of pathogenic pathways concerned with chemotaxis, immune mediators such as IL-1 and macrophage growth factors, key lymphocyte and fibroblast cell subpopulations, modulation of fibroblast number and matrix output and the interactions of endothelial and smooth muscle cells. Specific findings and hypotheses developed from our studies of animal models and lund cells will continue to be applied to our targeted patient population as we continue to seek novel ways of approaching their diagnosis and management. This includes monitoring of the mineral content of lavage fluids and cells as markers of long-term exposure history. The studies are significant in terms of the multidisciplinary, collaborative and vertical approaches that will be used to define the importance of a selected number of etiologic pathways that lead to pulmonary pathology related to occupational and immunologic lung disease.